Challenges and new prospects in hepatosplenic γδT-cell lymphoma

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoid neoplasms characterized by aggressive clinical behavior and dismal prognosis. Hepatosplenic gamma delta T-cell lymphoma (gamma delta-HSTL) is a particular form of PTCL that arises from a small subset of gamma/delta T-cellreceptor-expressing lymphocytes. gamma delta-HSTL has a rapidly progressive course and poor outcome due also to its refractoriness to conventional chemotherapy regimens. The very low incidence of gamma delta-HSTL, along with its propensity to mimic different pathological entities, makes this lymphoma a true diagnostic challenge. In this review, we highlight the biological and clinical features of gamma delta-HSTL that contribute to making this lymphoma a mostly incurable disease. Moreover, we provide a new insight into the crosstalk between HSTL clones and the bone marrow, liver and spleen vascular microenvironment, in which neoplastic cells reside and proliferate. We further discuss. gamma delta-HSTL associated molecules that might be proposed as potential targets for novel therapeutic approaches.